Computational investigation of blood cell transport in retinal microaneurysms

Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). MA leakage or rupture may precipitate local pathology in the surrounding neural retina that impacts visual function. Thrombosis in MAs may affect their turnover time, an indicator associated with visual and anatomic outcomes in the diabetic eyes. In this work, we perform computational modeling of blood flow in microchannels containing various MAs to investigate the pathologies of MAs in DR. The particle-based model employed in this study can explicitly represent red blood cells (RBCs) and platelets as well as their interaction in the blood flow, a process that is very difficult to observe in vivo. Our simulations illustrate that while the main blood flow from the parent vessels can perfuse the entire lumen of MAs with small body-to-neck ratio (BNR), it can only perfuse part of the lumen in MAs with large BNR, particularly at a low hematocrit level, leading to possible hypoxic conditions inside MAs. We also quantify the impacts of the size of MAs, blood flow velocity, hematocrit and RBC stiffness and adhesion on the likelihood of platelets entering MAs as well as their residence time inside, two factors that are thought to be associated with thrombus formation in MAs. Our results show that enlarged MA size, increased blood velocity and hematocrit in the parent vessel of MAs as well as the RBC-RBC adhesion promote the migration of platelets into MAs and also prolong their residence time, thereby increasing the propensity of thrombosis within MAs. Overall, our work suggests that computational simulations using particle-based models can help to understand the microvascular pathology pertaining to MAs in DR and provide insights to stimulate and steer new experimental and computational studies in this area.

Thirty-year Trends in Complications in U.S. Adults With Newly Diagnosed Type 2 Diabetes

<b>Objective:</b> To assess the prevalence of and trends in complications among US adults with newly diagnosed diabetes. <p><b>Research design and methods:</b> We included 1,486 nonpregnant adults (aged≥20 years) with newly diagnosed diabetes (diagnosed within the past 2 years) from the 1988-1994 and 1999-2018 National Health and Nutrition Examination Survey. We estimated trends in albuminuria (albumin-to-creatinine ratio≥30 mg/g), reduced estimated glomerular filtration rate (eGFR<60 ml/min/1.73 m²), retinopathy (any retinal microaneurysms or blot hemorrhages), and self-reported cardiovascular disease (history of congestive heart failure, heart attack, or stroke).</p> <p><b>Results: </b>From 1988-1994 to 2011-2018, there was a significant decrease in the prevalence of albuminuria (38.9 to 18.7%, p-for-trend<0.001), but no change in the prevalence of reduced eGFR (7.5 to 9.9%, p-for-trend=0.30), retinopathy (1988-1994 to 1999-2008 only; 13.2 to 12.1%, p-for-trend=0.86), or self-reported cardiovascular disease (19.0 to 16.5%, p-for-trend=0.64). There were improvements in glycemic, blood pressure, and lipid control in the population, and these partially explained the decline in albuminuria. Complications were more common at the time of diabetes diagnosis for adults who were older, lower income, less educated, and obese.</p> <p><b>Conclusion:</b> Over the past three decades, there have been encouraging reductions in albuminuria and risk factor control in adults with newly diagnosed diabetes. However, the overall burden of complications around the time of diagnosis remains high.</p>

Thirty-year Trends in Complications in U.S. Adults With Newly Diagnosed Type 2 Diabetes

<b>Objective:</b> To assess the prevalence of and trends in complications among US adults with newly diagnosed diabetes. <p><b>Research design and methods:</b> We included 1,486 nonpregnant adults (aged≥20 years) with newly diagnosed diabetes (diagnosed within the past 2 years) from the 1988-1994 and 1999-2018 National Health and Nutrition Examination Survey. We estimated trends in albuminuria (albumin-to-creatinine ratio≥30 mg/g), reduced estimated glomerular filtration rate (eGFR<60 ml/min/1.73 m²), retinopathy (any retinal microaneurysms or blot hemorrhages), and self-reported cardiovascular disease (history of congestive heart failure, heart attack, or stroke).</p> <p><b>Results: </b>From 1988-1994 to 2011-2018, there was a significant decrease in the prevalence of albuminuria (38.9 to 18.7%, p-for-trend<0.001), but no change in the prevalence of reduced eGFR (7.5 to 9.9%, p-for-trend=0.30), retinopathy (1988-1994 to 1999-2008 only; 13.2 to 12.1%, p-for-trend=0.86), or self-reported cardiovascular disease (19.0 to 16.5%, p-for-trend=0.64). There were improvements in glycemic, blood pressure, and lipid control in the population, and these partially explained the decline in albuminuria. Complications were more common at the time of diabetes diagnosis for adults who were older, lower income, less educated, and obese.</p> <p><b>Conclusion:</b> Over the past three decades, there have been encouraging reductions in albuminuria and risk factor control in adults with newly diagnosed diabetes. However, the overall burden of complications around the time of diagnosis remains high.</p>

Intravitreal aflibercept partially reverses severe non-proliferative diabetic retinopathy in treatment-naïve patients

Objective To evaluate whether diabetic retinopathy can be reversed after aflibercept, based on improvements in diabetic macular edema, hard exudates (HEs) of the posterior pole, and retinal microaneurysms (MAs). Methods This was a single-center retrospective study of 30 patients (34 eyes) with severe non-proliferative diabetic retinopathy (NPDR) who were treated between August and October 2018. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), area of HEs, and number of MAs were compared before and after treatment. Results The mean patient age was 61.4 ± 7.1 years; 14 patients (46.7%) were men. The mean number of injections per patient was 3.5 ± 0.5. The time between the last injection and the last follow-up was 82 days (range, 78–110 days). Six months after the first intravitreal injection, significant improvement was observed in BCVA (from 0.70 ± 0.18 to 0.42 ± 0.19 logMAR), CFT (from 377.17 ± 60.41 to 261.21 ± 31.50 µm), and number of MAs (from 182.2 ± 77.4 to 101.5 ± 59.6). Observations over 6 months after the first intravitreal injection showed a statistically significant reduction in the area of HEs (P = 0.007). No adverse events occurred during the treatment period. Conclusion Diabetic retinopathy might be partially reversed by aflibercept treatment, as indicated by BCVA, CFT, number of MAs, and area of HEs.

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). Vision can be reduced at any stage of DR by MAs, which may enlarge, rupture and leak fluid into the neural retina. Recent advances in ophthalmic imaging techniques enable reconstruction of the geometries of MAs and quantification of the corresponding haemodynamic metrics, such as shear rate and wall shear stress, but there is lack of computational models that can predict thrombus formation in individual MAs. In this study, we couple a particle model to a continuum model to simulate the platelet aggregation in MAs with different shapes. Our simulation results show that under a physiologically relevant blood flow rate, thrombosis is more pronounced in saccular-shaped MAs than fusiform-shaped MAs, in agreement with recent clinical findings. Our model predictions of the size and shape of the thrombi in MAs are consistent with experimental observations, suggesting that our model is capable of predicting the formation of thrombus for newly detected MAs. This is the first quantitative study of thrombosis in MAs through simulating platelet aggregation, and our results suggest that computational models can be used to predict initiation and development of intraluminal thrombus in MAs as well as provide insights into their role in the pathophysiology of DR.

Microaneurysms visualisation using five different optical coherence tomography angiography devices compared to fluorescein angiography

BackgroundTo compare fluorescein angiography (FA) and five different optical coherence tomography angiography (OCTA) devices and to test their reproducibility in the evaluation of retinal microaneurysms (MAs) secondary to diabetic retinopathy (DR).MethodsOn the same day, patients with DR were imaged with FA and five OCTA devices: prototype Spectralis OCTA, prototype PlexElite, RTVue XR Avanti, AngioPlex and DRI OCT Triton. For all OCTA devices, a 3×3 volume scan pattern was performed. MAs were evaluated for the superficial capillary plexus (SCP) and deep capillary plexus (DCP).ResultsTwenty eyes of 15 patients with DR were included. FA counted a significantly higher number of MAs compared to OCTA devices. Spectralis OCTA obtained a significantly higher number of MAs compared to PlexElite, RTVue XR Avanti, AngioPlex and DRI OCT Triton (p<0.0001). PlexElite and AngioPlex showed a greater number of MAs in the SCP, Spectralis OCTA, RTVue XR Avanti and DRI OCT Triton in the DCP. Higher sensitivity (43.3%) but lowest specificity (54.4%) was observed for Spectralis OCTA compared to other devices. The higher specificity (78.5%) and positive predictive value (83.3%) were observed for DRI OCT Triton.ConclusionsFA remains the best imaging modality to visualise retinal MAs. Spectralis OCTA was able to detect more MAs compared to other devices, likely due to the higher number of B-scans in the scanned area as well as due to the higher number of repeated B-scans. The high variability between OCTA devices should be taken into account for future clinical trials as in clinical practice.